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Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors

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Item Type:Article
Title:Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors
Creators Name:Temido-Ferreira, M. and Ferreira, D.G. and Batalha, V.L. and Marques-Morgado, I. and Coelho, J.E. and Pereira, P. and Gomes, R. and Pinto, A. and Carvalho, S. and Canas, P.M. and Cuvelier, L. and Buée-Scherrer, V. and Faivre, E. and Baqi, Y. and Müller, C.E. and Pimentel, J. and Schiffmann, S.N. and Buée, L. and Bader, M. and Outeiro, T.F. and Blum, D. and Cunha, R.A. and Marie, H. and Pousinha, P.A. and Lopes, L.V.
Abstract:Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca(2+) influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity.
Source:Molecular Psychiatry
ISSN:1359-4184
Publisher:Nature Publishing Group (U.K.)
Date:27 June 2018
Official Publication:https://doi.org/10.1038/s41380-018-0110-9
PubMed:View item in PubMed

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